Colonization of and adhesion to the mammalian small intestine by enterotoxigenic Escherichia coli (ETEC) is a necessary prerequisite for the production of ETEC induced diarrheal disease and is mediated by specific bacterial pili. It is proposed to study the mechanism(s) that facilitate colonization of the small intestine by ETEC. The experimental design will be divided into three separate but highly interrelated areas. Part one will emphasize the study of the genetic organization and the regulation of expression of pili associated with colonization. Included in this part will be the definition of those conditions that maximize pilus expression and the development or modification of procedures to reproducibly identify these pilus adhesive factors. Part two will emphasize the structure and function of adhesive pili. A comparative examination of the chemical and physical properties of pili and the study of their interactions in vitro with receptors on epithelial cells isolated from small intestines will be performed. Substances that block adhesion will be identified. The third part will emphasize a search for other yet undescribed, antigenically different pili that appear to facilitate colonization of human small intestines.